Abrogation of STAT3 activation cascade by Ginkgolide C mitigates
tumorigenesis in lung cancer preclinical model
Abstract
Background and purpose: Ginkgolide C (GGC) isolated form Ginko biloba
(Ginkgoaceae) leaf can demonstrate pleiotropic pharmacological actions
although. its anti-oncogenic impact in non-small cell lung cancer
(NSCLC) model has not been reconnoitered. As signal transducer and
activator of transcription 3 (STAT3) cascade can promote tumor growth
and survival, we contemplated that GGC may interrupt this signaling
cascade to expend its anti-cancer actions in NSCLC. Experimental
approach: The effect of GGC on STAT3 activation, associated protein
kinases, STAT3-regulated gene products, cellular proliferation, and
apoptosis was examined. The in vivo effect of GGC on the growth of human
NSCLC xenograft tumors in athymic nu/nu female mice was also
investigated. Key results: GGC attenuated the phosphorylation of STAT3
and varying upstream kinases effectively. Exposure to pervanadate
modulated GGC-induced down-regulation of STAT3 activation and promoted
an elevation in the level of PTP protein. Indeed, silencing of the
PTPgene reversed the GGC-promoted abrogation of STAT3 activation and
apoptosis. Moreover, GGC exposure significantly reduced NSCLC tumor
growth without demonstrating significant adverse effects via decreasing
levels of p-STAT3 in mice tissues. Conclusions and Implications:
Overall, the findings support that GGC may exhibit anti-neoplastic
actions by mitigation of STAT3 signaling cascade in NSCLC.